{
  "abstract": "Tumor incidence increases markedly with advancing age, yet the molecular mechanisms linking aging-driven senescence to tumorigenesis remain incompletely understood. The proteasome activator PA200 preserves genomic stability by mediating the degradation of acetylated histones during aging. However, its function in age-associated tumor progression is poorly defined. Here, we demonstrate that PA200 promotes aging-associated tumorigenesis independent of its histone-degrading activity. Elevated PA200 correlates with poor prognosis and advancing age in human lung cancer. PA200-deficient tumor cells exhibit suppressed proliferation and migration, accompanied by aggravated oxidative-stress-triggered cellular senescence. Mechanistically, p53 directly binds and represses PSME4 transcription at its promoter. Reciprocally, PA200 facilitates proteasomal degradation of β-catenin, thereby sustaining p53 activity and forming a negative feedback loop. In the urethane-induced mouse lung tumor model, PA200 ablation markedly reduces tumor burden, especially in middle-aged mice. This effect is coupled with β-catenin accumulation, lowered p53 levels, and partial remodeling of the pro-inflammatory tumor microenvironment. Our findings uncover the p53-PA200-β-catenin feedback axis as a key driver of age-dependent lung tumorigenesis and highlight PA200 as a potential therapeutic target for elderly patients with lung cancer.",
  "abstract_shown": true,
  "affiliations": [
    "Ministry of Education Key Laboratory of Cell Proliferation & Regulation Biology, College of Life Sciences, Beijing Normal University, 19 Xinjiekouwai Avenue, Beijing 100875, China"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Chen-Yang Jiang",
      "orcid": "0009-0007-6492-6047"
    },
    {
      "affs": [
        0
      ],
      "name": "Yan-Li Wang"
    },
    {
      "affs": [
        0
      ],
      "name": "Nan Lv"
    },
    {
      "affs": [
        0
      ],
      "name": "Bing-Kun Cai"
    },
    {
      "affs": [
        0
      ],
      "name": "Tian-Xia Jiang",
      "orcid": "0000-0001-6344-8214"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/ctjeykdrn128e.bib",
  "cited_by": 0,
  "doi": "10.3390/ijms27198783",
  "fulltext_url": "https://europepmc.org/articles/PMC13665431",
  "id": "ctjeykdrn128e",
  "issns": [
    "1422-0067"
  ],
  "landing_url": "https://www.mdpi.com/1422-0067/27/19/8783",
  "language": "eng",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2730|Cancer-related Molecular Pathways"
    ]
  ],
  "openalex": "W7214926003",
  "pdf_url": "https://europepmc.org/articles/PMC13665431?pdf=render",
  "pmcid": "PMC13665431",
  "pmid": "42884025",
  "published": "2026-09-30",
  "publisher": "MDPI AG",
  "ris": "https://research.draconitic.com/paper/ctjeykdrn128e.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:55Z",
      "native_id": "10.3390/ijms27198783",
      "source": "crossref",
      "url": "https://www.mdpi.com/1422-0067/27/19/8783"
    },
    {
      "first_seen": "2026-10-30T12:19:16Z",
      "native_id": "MED:42884025",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42884025"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2730|Cancer-related Molecular Pathways",
      "subfield": "oncology"
    }
  ],
  "title": "The p53-PA200 Feedback Loop Modulates Age-Dependent Tumorigenesis",
  "title_text": "The p53-PA200 Feedback Loop Modulates Age-Dependent Tumorigenesis",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:16Z",
  "url": "https://research.draconitic.com/paper/ctjeykdrn128e",
  "venue": "International Journal of Molecular Sciences",
  "versions": []
}